Cancer Chemother Phan'nacol (1992) 31 (Suppl I): S 115 - S t 18
ancer hemotherapyand harmacology 9 Springer-Verlag 1992
Radiotherapy of cholangioearcinoma: the roles for primary and adjuvant therapies Takeki Shiinal, Shuichi Mikuriyal, Takashi Un01, Takafumi Toital, Seiichi Serizawal, Jun Itamil, Saburo Kawai2, and Masanao Tani 2 1 Department of Radiotherapy and Oncology, and 2 Department of Surgery, National Medical Center Hospital, Tokyo, Japan
Summary. A total of 22 patients with cholangiocarcinoma who had been treated with external radiotherapy between 1978 and 1989 were analyzed. Of the 22 patients, 18 had cancer of the hepatic hilus (Klatskin) and 4 had intrahepatic biliary cancer; all but 2 of the subjects had advanced disease. In all, 16 patients underwent primary irradiation for unresectable tumors, 4 were subjected to adjuvant irradiation after gross tumor resection, and 2 received preoperative irradiation followed by gross tumor resection. The mean initial irradiation dose was 52.0 Gy (range, 26-78 Gy). The TDF (time-dose-fractionation) for the entire course of radiotherapy ranged from 49 to 154 (mean, 100). The median survival of all patients was 10 months, and the cumulative 1-year survival value was 37.7%. The external radiotherapy proved to be effective in the treatment of cholangiocarcinoma in terms of palliation and survival.
Introduction Despite recent advances in diagnostic imaging modalities such as ultrasound (US) and computed tomography (CT), most patients with cholangiocarcinoma have advanced disease at diagnosis and tumor resectability is low. Furthermore, even after curative resection has been performed, the local reccurence rate is high and the prognosis remains poor. Adenocarcinoma has long been considered to be radioresistant, but some recent reports justify the use of radiotherapy for bile duct cancer. External radiotherapy has been applied solely or in combination with brachyther-
apy. The objective of the present study was to assess the value of external radiotherapy as locoregional therapy for cholangiocarcinoma.
Patients and methods Patients. A total of 22 patients with cholangiocarcinoma were referred to the Department of Radiotherapy at the National Medical Center Hospital between 1978 and 1989. Patients with a history of postoperative recurfence and those who had received less than 20 Gy were excluded from this study. The histological diagnosis of 15 patients was adenocarcinoma; materials for tissue diagnosis were not obtained from the remaining 7 subjects. The 22 patients included 14 men and 8 women whose mean age was 63.5 years (range, 4 5 - 85 years) and who had been diagnosed as having intrahepatic cholangiocarcinoma (n = 4) or hilar cholangiocarcinoma (Klatsldn tumor, n = 18). Two patients had localized disease, but the others all had advanced disease. The patients' characteristics are summarized in Table 1. Treatment. In all, 16 patients underwent primary irradiation for unresectable tumors in the presence or absence of palliative surgery, 4 were subjected to primary irradiation after gross tumor resection, and 2 received preoperative irradiation followed by gross tumor resection. All patients were treated with high-energy (6-, 10-, or 18-MV) X-rays. The initial dose varied between 26 and 78 Gy (78 Gy was the combined dose of preoperative and postoperative irradiation), the mean value being 52.0 Gy. AP-PA parallel opposed fields were used, with the field size ranging from 16 ( 4 x 4 ) to 162 (12x 13.5) cm 2 and the average being 61.8 cm 2. The patients tolerated the radiotherapy well, and four subjects
Table 1. Patients' characteristics and treatment Characteristic
Hepatic hilus
Sex (M/F)
10/8
Mean age in years (range)
63.0 ( 4 5 - 85)
Resection (n) * Presented at the Second International Symposium on Treatment of Liver Cancer. Taipei, 3 - 4 February 1991 Correspondence to: Takeki Shiina, Department of Radiotherapy and Oncology, National Medical Center Hospital, 1-21-1 Toyama, Shinjukuku, Tokyo 162 Japan
4
Initial radiotherapy: Dose (Gy) 50.9 (26-78) Field size (cm 2) 58.8 (16-162) TDF (totalcourse)
97.9 (49-154)
Intrahepatic 4/0 65.5 (46-78) 2 56.8 (45-64) 76.0 (36-121) 110.3 (85-152)
Total 14/8 63.5 •
9.9
6 52.0 • 12.6 61.8 • 32.3 100
• 25
Sl16 100-] 9080-
9 : ~>TDF 100 ( n = l O ) 9 : < T D F 100 ( n = 1 2 )
80
70-
>~ 70
60.
60
50.
56 40
40. 30.
30
20-
o.
20
10-
,0
0
0
560
15'00
I 0'00
II 500
DAYS
Fig. 1. Cumulative survival curve generated for patients with cholangiocarcinoma (n = 22)
100 9000>
I--
O
,,=,
9 :resection(+) (n=6) 9 :resection(--) (n=16)
70-
6050-
40ao-
=" 2010-
s6o
lO'OO
ls'oo
1000 DAYS
1__,
15oo
DAYS
Fig. 2. Cumulative survival curves constructed for cholangiocarcinoma patients treated in the presence and absence of gross tumor resection
received additional irradiation (36-53 Gy; mean, 45.5 Gy) for palliation. For purposes of comparison, we performed time-dose-fractionation (TDF) conversion on all radiation doses. The TDF for the entire course of radiotherapy ranged from 49 to 154 (mean, 100). The usefulness of this therapy was evaluated on the basis of its feasibility, the local response, the patients' survival, and the postmortem examination findings.
Results
Feasibility The initial external radiotherapy was well tolerated by the patients, and radiotherapy was discontinued under 40 Gy in only four subjects due to nausea and vomiting in two cases and to cholangitis in one case. The acute side effects of the radiotherapy were minimal except in these three patients. In one other case, the primary irradiation was altered to preoperative irradiation with 31 Gy.
Local response The responsiveness to the external irradiation was evaluated by pre- and posttreatment cholangiograms. In all, 14 patients were evaluable, and improvement on the cholangiogram was noted in 7 subjects (50%). One patient
Fig. 3. Cumulative survivaI curves generated for cholangiocarcinoma cases as a function of the TDF
1009080706050403020100
9 : ->60cm 2 (n=8) 9 :
ancer hemotherapyand harmacology 9 Springer-Verlag 1992
Radiotherapy of cholangioearcinoma: the roles for primary and adjuvant therapies Takeki Shiinal, Shuichi Mikuriyal, Takashi Un01, Takafumi Toital, Seiichi Serizawal, Jun Itamil, Saburo Kawai2, and Masanao Tani 2 1 Department of Radiotherapy and Oncology, and 2 Department of Surgery, National Medical Center Hospital, Tokyo, Japan
Summary. A total of 22 patients with cholangiocarcinoma who had been treated with external radiotherapy between 1978 and 1989 were analyzed. Of the 22 patients, 18 had cancer of the hepatic hilus (Klatskin) and 4 had intrahepatic biliary cancer; all but 2 of the subjects had advanced disease. In all, 16 patients underwent primary irradiation for unresectable tumors, 4 were subjected to adjuvant irradiation after gross tumor resection, and 2 received preoperative irradiation followed by gross tumor resection. The mean initial irradiation dose was 52.0 Gy (range, 26-78 Gy). The TDF (time-dose-fractionation) for the entire course of radiotherapy ranged from 49 to 154 (mean, 100). The median survival of all patients was 10 months, and the cumulative 1-year survival value was 37.7%. The external radiotherapy proved to be effective in the treatment of cholangiocarcinoma in terms of palliation and survival.
Introduction Despite recent advances in diagnostic imaging modalities such as ultrasound (US) and computed tomography (CT), most patients with cholangiocarcinoma have advanced disease at diagnosis and tumor resectability is low. Furthermore, even after curative resection has been performed, the local reccurence rate is high and the prognosis remains poor. Adenocarcinoma has long been considered to be radioresistant, but some recent reports justify the use of radiotherapy for bile duct cancer. External radiotherapy has been applied solely or in combination with brachyther-
apy. The objective of the present study was to assess the value of external radiotherapy as locoregional therapy for cholangiocarcinoma.
Patients and methods Patients. A total of 22 patients with cholangiocarcinoma were referred to the Department of Radiotherapy at the National Medical Center Hospital between 1978 and 1989. Patients with a history of postoperative recurfence and those who had received less than 20 Gy were excluded from this study. The histological diagnosis of 15 patients was adenocarcinoma; materials for tissue diagnosis were not obtained from the remaining 7 subjects. The 22 patients included 14 men and 8 women whose mean age was 63.5 years (range, 4 5 - 85 years) and who had been diagnosed as having intrahepatic cholangiocarcinoma (n = 4) or hilar cholangiocarcinoma (Klatsldn tumor, n = 18). Two patients had localized disease, but the others all had advanced disease. The patients' characteristics are summarized in Table 1. Treatment. In all, 16 patients underwent primary irradiation for unresectable tumors in the presence or absence of palliative surgery, 4 were subjected to primary irradiation after gross tumor resection, and 2 received preoperative irradiation followed by gross tumor resection. All patients were treated with high-energy (6-, 10-, or 18-MV) X-rays. The initial dose varied between 26 and 78 Gy (78 Gy was the combined dose of preoperative and postoperative irradiation), the mean value being 52.0 Gy. AP-PA parallel opposed fields were used, with the field size ranging from 16 ( 4 x 4 ) to 162 (12x 13.5) cm 2 and the average being 61.8 cm 2. The patients tolerated the radiotherapy well, and four subjects
Table 1. Patients' characteristics and treatment Characteristic
Hepatic hilus
Sex (M/F)
10/8
Mean age in years (range)
63.0 ( 4 5 - 85)
Resection (n) * Presented at the Second International Symposium on Treatment of Liver Cancer. Taipei, 3 - 4 February 1991 Correspondence to: Takeki Shiina, Department of Radiotherapy and Oncology, National Medical Center Hospital, 1-21-1 Toyama, Shinjukuku, Tokyo 162 Japan
4
Initial radiotherapy: Dose (Gy) 50.9 (26-78) Field size (cm 2) 58.8 (16-162) TDF (totalcourse)
97.9 (49-154)
Intrahepatic 4/0 65.5 (46-78) 2 56.8 (45-64) 76.0 (36-121) 110.3 (85-152)
Total 14/8 63.5 •
9.9
6 52.0 • 12.6 61.8 • 32.3 100
• 25
Sl16 100-] 9080-
9 : ~>TDF 100 ( n = l O ) 9 : < T D F 100 ( n = 1 2 )
80
70-
>~ 70
60.
60
50.
56 40
40. 30.
30
20-
o.
20
10-
,0
0
0
560
15'00
I 0'00
II 500
DAYS
Fig. 1. Cumulative survival curve generated for patients with cholangiocarcinoma (n = 22)
100 9000>
I--
O
,,=,
9 :resection(+) (n=6) 9 :resection(--) (n=16)
70-
6050-
40ao-
=" 2010-
s6o
lO'OO
ls'oo
1000 DAYS
1__,
15oo
DAYS
Fig. 2. Cumulative survival curves constructed for cholangiocarcinoma patients treated in the presence and absence of gross tumor resection
received additional irradiation (36-53 Gy; mean, 45.5 Gy) for palliation. For purposes of comparison, we performed time-dose-fractionation (TDF) conversion on all radiation doses. The TDF for the entire course of radiotherapy ranged from 49 to 154 (mean, 100). The usefulness of this therapy was evaluated on the basis of its feasibility, the local response, the patients' survival, and the postmortem examination findings.
Results
Feasibility The initial external radiotherapy was well tolerated by the patients, and radiotherapy was discontinued under 40 Gy in only four subjects due to nausea and vomiting in two cases and to cholangitis in one case. The acute side effects of the radiotherapy were minimal except in these three patients. In one other case, the primary irradiation was altered to preoperative irradiation with 31 Gy.
Local response The responsiveness to the external irradiation was evaluated by pre- and posttreatment cholangiograms. In all, 14 patients were evaluable, and improvement on the cholangiogram was noted in 7 subjects (50%). One patient
Fig. 3. Cumulative survivaI curves generated for cholangiocarcinoma cases as a function of the TDF
1009080706050403020100
9 : ->60cm 2 (n=8) 9 :
